The proposed work deals with the determination of the antigenic structure of human adult hemoglobin (Hb) and with probing the molecular and immunobiological factors which determine and regulate the antigenicity of the antigenic sites of myoglobin (Mb). For determination of the antigenic structure of Hb, chemical derivatives of the protein, modified at specific amino acid locations, will be prepared and their conformation and immunochemistry studied. A variety of long and overlapping peptides will be prepared by various chemical and enzymic cleavage procedures and their specific interaction with antisera to the native protein determined. Further narrowing down of regions will be achieved by studying chemical derivatives of various immunochemically reactive peptides. Having narrowed down the regions to a conveniently small size, final delineation will be achieved by the immunochemistry of synthetic peptides corresponding to various parts of the regions. Antibodies against coupled intact antigenic sites will be prepared and studied. Having established the entire antigenic structure of sperm-whale Mb with early course antisera raised in rabbits and goats, it will now be determined whether the antigenic expression of the Mb molecule, in terms of its antibody specificity and immunodominance of its sites, will show any changes with time after immunization and with the species in which the antisera are raised. The factors conferring antigenicity on the Mb antigenic sites will be investigated. The molecular specificity of autoantibodies to myoglobin in humans and rabbits will be studied and the genetic control of the immune response to the antigenic sites of Mb in mice will be determined.